The ICSD-3 and DSM-5 guidelines for diagnosing narcolepsy: clinical relevance and practicality

Abstract

Narcolepsy is a chronic neurological disease manifesting as difficulty with maintaining continuous wake and sleep. Clinical presentation varies but requires excessive daytime sleepiness (EDS) occurring alone or together with features of rapid-eye movement (REM) sleep dissociation (e.g., cataplexy, hypnagogic/hypnopompic hallucinations, sleep paralysis), and disrupted nighttime sleep. Narcolepsy with cataplexy is associated with reductions of cerebrospinal fluid (CSF) hypocretin due to destruction of hypocretin peptide-producing neurons in the hypothalamus in individuals with a specific genetic predisposition. Updated diagnostic criteria include the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and International Classification of Sleep Disorders Third Edition (ICSD-3). DSM-5 criteria require EDS in association with any one of the following: (1) cataplexy; (2) CSF hypocretin deficiency; (3) REM sleep latency ≤15 minutes on nocturnal polysomnography (PSG); or (4) mean sleep latency ≤8 minutes on multiple sleep latency testing (MSLT) with ≥2 sleep-onset REM-sleep periods (SOREMPs). ICSD-3 relies more upon objective data in addition to EDS, somewhat complicating the diagnostic criteria: 1) cataplexy and either positive MSLT/PSG findings or CSF hypocretin deficiency; (2) MSLT criteria similar to DSM-5 except that a SOREMP on PSG may count as one of the SOREMPs required on MSLT; and (3) distinct division of narcolepsy into type 1, which requires the presence of cataplexy or documented CSF hypocretin deficiency, and type 2, where cataplexy is absent, and CSF hypocretin levels are either normal or undocumented. We discuss limitations of these criteria such as variability in clinical presentation of cataplexy, particularly when cataplexy may be ambiguous, as well as by age; multiple and/or invasive CSF diagnostic test requirements; and lack of normative diagnostic test data (e.g., MSLT) in certain populations. While ICSD-3 criteria reflect narcolepsy pathophysiology, DSM-5 criteria have greater clinical practicality, suggesting that valid and reliable biomarkers to help standardize narcolepsy diagnosis would be welcomed.

Brain Networks and Dynamics in Narcolepsy

“…It is also common for patients to suffer from sleep disturbances, like frequent awakenings and dissociated REM sleep [12] where the REM sleep will follow shortly after falling asleep instead of after a period of deep sleep. In fact, a socalled multiple sleep latency test (MSLT), where the time until entering REM sleep is measured is part of the diagnostic criteria [10] . Typical onset is from adolescence until early adulthood but there are also cases of narcolepsy in very young children [13] , and some reports suggest that it may be even more common in preadolescence than previously considered.…”

“…During REM sleep, the brain becomes more active and it is also when most of the dreaming occurs, and voluntary muscles are immobilised to prevent movement during dreaming [9] . Sleep in narcolepsy is characterised by sleep onset REM periods (SOREMP), which are REM sleep periods that happen within 15 minutes of falling asleep [10], [11] and frequent awakenings throughout the night ( Figure 1B). 2.…”

Quickly diagnosed and treated prepubertal Type 1 narcolepsy case

“…DSM-5 criteria require EDS in association with any one of the following: cataplexy; cerebrospinal fluid (CSF) hypocretin deficiency; rapid eye movement (REM) sleep latency ≤15 min on nocturnal polysomnography (PSG); or mean sleep latency ≤8 min on multiple sleep latency testing (MSLT) with ≥2 sleep-onset REM sleep periods (SOREMPs) [2]. But only 10% of patients have all the classical narcoleptic tetrad.…”

“…The prevalence of narcolepsy in the paediatric population remains unknown, but based upon the regional study conducted in the U.S.A., it could affect 20-50 per 100,000 children [5]. Two peaks of onset are suggested, at ages 15-25 years and ages 30-35 years [2]. Cataplexy is pathognomonic for narcolepsy.…”

Polycystic Ovarian Syndrome and Narcolepsy: A Coincidental Relationship?

“…Some individuals with narcolepsy have associated low or deficient hypocretin, a brain peptide that helps maintain alertness and regulates rapid eye movement sleep cycles. In the international classification of sleep disorders -third edition [1], two types of narcolepsy exists: type 1 is di-ly pubarche and thelarche [4]. Researchers found a lower serum hypocretin in 36 women with PCOS compared to the control group [5].…”